Synthesis, density functional theory calculation, molecular docking studies, and evaluation of novel 5-nitrothiophene...

Within the scope of this study, new 2-{2-[(5-nitrothiophen-2-yl)methylene]hydrazinyl}thiazole derivatives (2a-j) were synthesized and investigated for their potential anticancer and enzyme inhibition activities. Spectroscopic techniques were used to determine the structures of substances. The anticancer activities of compounds were detected in A549 human lung carcinoma and L929 murine fibroblast cell lines, determining cytotoxicity, apoptosis, mitochondrial membrane integrity, and caspase-3 activation. Compounds 2b bearing 4-nitrophenyl, 2c bearing phenyl, and 2d bearing 4-cyanophenyl moieties were specified with high anticancer activity, acting through an apoptotic pathway with an apoptosis ratio of 9.61%-15.59%. Mitochondrial membrane depolarization was determined to be 25.53% and 22.33% for compounds 2b and 2c, respectively. Furthermore, compound 2c exhibited excellent caspase-3 activation. A molecular docking study was realized with compound 2c on the caspase-3 enzyme. Furthermore, the electronic characteristics of the active compounds were investigated using density functional theory (DFT) at the B3LYP/6-31G (d, p) level. The frontier molecular orbital energy and atomic net charges were examined.